Chiral 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid and precursors and preparation thereof

Abstract

The instant invention relates to optically pure, L-(S)forms of 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid compounds and their method of preparation from optionally pure L-phenylalanine precursor compounds and their preparation utilizing novel in situ cationic catalyst systems.

What is claimed is: 
     
       1. A method of producing an optically pure compound comprising L(S)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid represented by the formula: ##STR6## wherein R 1  and R 2  are independently hydrogen, lower alkyl, lower alkoxy, lower alkylthio, lower alkylsulfinyl, lower alkylsulfonyl, hydroxy or R 1  and R 2  together are methylenedioxy, comprising: (a) hydrogenating, in the presence of an in situ cationic catalyst comprising: (1) a chiral phosphine ligand; and   (2) [M(Diene) 2  ] +  X -  wherein M is selected from the group consisting of Rh, Ru, Pt, Pd, and Ni, Diene is norbornadiene or cyclooctadiene, and X -  is selected from the group consisting of PF 6  --, ClO 4  --, and BF 4  --; a primary precursor compound represented by the formula: ##STR7##  to produce a hydrogenated compound represented by the formula: ##STR8##  wherein R' is H or CH 3  and R is C 6  H 5  or CH 3  ; (b) hydrolyzing the hydrogenated compound to produce an optically pure amino acid salt; and     (c) performing a Pictet-Spengler ring closure of the amino acid salt to yield the optically pure L(S)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid compound.   
     
     
       2. The method of claim 1 wherein the chiral phosphine ligand is (R)--(+)--2,2'-bis(diphenylphosphino)-1,1'-binaphthyl. 
     
     
       3. The method of claim 1 wherein the chiral phosphine ligand is (R)--(+)--1,2-bis(diphenylphosphino)propane. 
     
     
       4. The method of claim 1 wherein the catalyst component (b) is [Rh(C 7  H 8 ) 2  ]+X - . 
     
     
       5. The method of claim 4 wherein X -  is PF 6`-- . 
     
     
       6. The method of claim 1 wherein the chiral phosphine ligand is selected from the group consisting of CHIRAPHOS, DIPAMP, NORPHOS, DIOP, CAMPHOS and DIOXOP. 
     
     
       7. The method of claim 1 wherein catalyst component (a) is ((R)--(+)-- 1,2-bis(diphenylphosphino)propane and catalyst component (b) is [Rh(C 7  H 8 ) 2  ]+PF 6  --. 
     
     
       8. Optically pure compound L(S)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid is prepared according to the method of claim 1. 
     
     
       9. A method of producing an optically pure L-phenylalanine compound represented by the formula comprising: ##STR9## by hydrogenating, in the presence of an in situ cationic catalyst comprising: (a) a chiral phosphine ligand; and   (b) [M(Diene) 2  ] +  X -  wherein M is selected from the group consisting of Rh, Ru, Pt, Pd and Ni Diene is norbornadiene or cyclooctadine, X -  is selected from the group consisting of PF 6  --, ClO 4  --, and BF 4  --; a precursor compound represented by the formula: ##STR10##  wherein R 1  and R 2  are independently hydrogen, lower alkyl, lower alkoxy, lower alkylthio, lower alkylsulfinyl, lower alkylsulfonyl, hydroxy or R 1  and R 2  together are methylenedioxy, R' is H or CH 3  and R is C 6  H 5  or CH 3 .   
     
     
       10. The method of claim 9 wherein the chiral phosphine ligand is (R)--(+)--2,2'-bis(diphenylphosphino)-1,1'-binaphthyl. 
     
     
       11. The method of claim 9 wherein the chiral phosphine ligand is (R)--(+)--1,2-bis(diphenylphosphino)propane. 
     
     
       12. The method of claim 9 wherein the chiral phosphine ligand is selected from the group consisting of CHIRAPHOS, DIPAMP, NORPHOS, DIOP, CAMPHOS and DIOXOP. 
     
     
       13. The method of claim 11 wherein the catalyst component (b) is [Rh(C 7  H 8 ) 2  ]+PF 6  --. 
     
     
       14. The method of claim 9 wherein the L-phenylalanine compound is selected from the group consisting of L-N-acetyl-3,4-dimethoxyphenylalanine, L-methyl-N-acetyl-3,4-dimethoxyphenylalanine, L-N-benzoyl-3,4-dimethoxyphenylalanine and L-methyl-N-benzoyl-3,4dimethoxyphenylalanine. 
     
     
       15. The method of claim 14 wherein the L-phenylalanine compound produced is enriched by recrystallization.